Technology Trends

The Wellcome Trust Sanger Institute is one of the largest genomics data centers in the world. In “The Hum and the Genome,” the Scientist writes about the IT infrastructure needed to handle the avalanche of data that researchers have to analyze. With its 2,000 processors and its 300 terabytes of storage, the data center uses today about 0.75 megawatts (MW) of power at a cost of €140,000 per year (about $170K). But the data center will need more than a petabyte of storage within three years, and its yearly electricity bill will reach €500,000 (more than $600K) for about 1.4 MW, enough to power more than a thousand homes. Read more…

Below is a small diagram showing the current IT infrastructure of the Wellcome Trust Sanger Institute, used by the Human Genome Project (Credit: Wellcome Trust Sanger Institute).

Here is a link to a larger version of this chart.

Now, let’s look at this IT infrastructure in detail.

• Computers




• Today: The datacenter hosts about 2,000 Alpha processors, originally designed by Digital Equipment (DEC), before its acquisition by Compaq, and later by Hewlett-Packard (HP).


• Tomorrow: The Sanger Institute is looking at cheaper solutions, especially now that HP has officially stopped any development on the Alpha front.


• Storage




• Today: Three different computer rooms have a total capacity of about 300 terabytes.


• Tomorrow: The IT management forecasts about a petabyte within three years — at least.


• Databases




• Today: There are about 40 different databases, and only two of them are in the 50 terabytes area.


• Tomorrow: One of the databases, the Trace sequence archive currently contains about 700 million entries, and it doubles every 10 months.


• Power bills




• Today: The current equipment needs about 0.75 megawatts for a cost of €140,000 per year (about $170K).


• Tomorrow: The new setup will need about 1.4 megawatts, which will raise the yearly bill to about €500,000 (about $615K today).

The supercomputer vendors can say all they want about diminishing costs. But they almost never talk about the power bills…

Sources: Stuart Blackman, The Scientist, Volume 19, Issue 11, Page 15, June 6, 2005; and various websites

Related stories can be found in the following categories.

• Databases
  


• Energy
  


• Genetics
  


• IT
  


• Storage
  


• Supercomputers
  

The Barbary Apes who live on Gibraltar’s Rock are the only semi-wild monkeys in Europe. And for decades, nobody knew where they came from. Now, after studying mitochondrial DNA from 280 individual samples, an international group of scientists from Germany, Switzerland and the U.S. has solved the mystery of the origin of Gibraltar’s macaques. Their study reveals that they descended from founders picked in both Morocco and Algeria. Of course, another mystery needs to be solved. You might not know that a local story says that if the monkeys disappear from Gibraltar, so will the British. So when the population of these Barbary Apes was almost reduced to zero sixty years ago, did British Prime Minister Winston Churchill order to capture some of them in nearby Africa? Read more…

Before going further, here is a great photograph of one of these Gibraltar’s Barbary Apes.

Now, let’s return to this news release from the Field Museum in Chicago.

An analysis of mitochondrial DNA from 280 individual samples reveals that the macaques on Gibraltar descended from founders taken from forest fragments in both Morocco and Algeria. The embargoed research will be published in the Early Edition of the Proceedings of the National Academy of Sciences (http://www.pnas.org/papbyrecent.shtml) .

[Note: this research should have been published online on April 25, 2005 by the Proceedings of the National Academy of Sciences, but is not yet available.]

Now, here are some more scientific details.

In mammals, mitochondrial DNA is inherited exclusively from the female, so it can be analyzed to determine matrilineal origins. This is especially relevant with mammals, such as macaques, that practice female philopatry, a social system in which females remain in their birth groups while males migrate between groups.

The research first identified 24 different haplotypes in the Algerian and Moroccan colonies of macaques. Each mitochondrial haplotype is identified by means of a specific DNA sequence.

Since the Algerian and Moroccan haplotypes are clearly distinct, evidence of any given haplotype in the mitochondrial DNA of Gibraltar macaques would indicate that they descended from the geographical population with that haplotype. [...] In fact, both Algerian and Moroccan haplotypes were found among the Gibraltar macaques, indicating that the Gibraltar colony was founded by female macaques from both regions.

The study is still speculating about when these apes were introduced in Gibraltar.

Some scientists believe the Barbary macaques were first brought to Gibraltar by the Moors, who occupied Spain between 711 and 1492. On the other hand, it’s possible that the original Gibraltar macaques were a remnant of populations that had spread throughout Southern Europe during the Pliocene, up to 5.5 million years ago.

So was it 5 million years ago or 60 years ago? A future study will tell.

In the mean time, you might want to read two additional pages from Wikipedia about Gibraltar and the Barbary Ape.

Sources: The Field Museum news release, April 25, 2005; and various websites

Related stories can be found in the following categories.

• Biotechnology
  
  
• DNA
  
  
• Genetics
  
  
• History
  
  
• Nature
  

There are many articles in the press today about the cloning of a champion endurance horse named Pieraz. I want to give my “Best Title of the Month” award to News24, in South Africa, for “Castrated horse becomes dad.” This is true, Pieraz, as most endurance horses, those engaged in races of up to 50 kilometers, was castrated. But its clone, created by Italian and French scientists, and called Pieraz-Cryozootech-Stallion, will be different from the original horse. It might not be able to race, but it will be put to stud to breed other horses within two years. Read more…

Before going further, here are two pictures of the champion horse and his young clone (Credit: Cryozootech).

On the left, you can see Pieraz, ridden by Valerie Kanavy, who was the owner and the trainer of the horse. On the right, Eric Palmer, from Cryozootech, is talking with Pieraz’s clone.

You might also want to look at this short video of Pieraz-Cryozootech-Stallion (RealAudio format, 71 seconds).

Now, here are some details from an article by New Scientist, “First clone of champion racehorse revealed.”

Like most endurance racehorses, Pieraz was castrated young and so cannot breed. The idea of cloning him was to “recreate his testicles” for breeding purposes, says Eric Palmer of Cryozootech, a company based in Paris, France, which supported Galli’s latest cloning work.

[Notes: Cesare Galli produced both horses at the University of Bologna in Cremona, Italy; and Cryozootech is based in Sonchamp, near Paris.]

“The plan is to make this horse a stallion,” says Palmer, and the clone will be mature enough to breed within two years. But although the new clone is Pieraz’s genetic twin, he says there is no guarantee that it will perform as well as the champion racehorse. Environmental factors could be crucial.

Cryozootech has ambitious plans, and wants to clone more than thirty other horses specialized in dressage or jumping. But it’s not that simple. The new foal was the only one which came alive, from 34 embryos implanted into 12 foster mothers.

In “Champion endurance horse cloned,” BBC News gives other details, picking some facts from this Cryozootech press release (PDF format, 1 page).

The new clone, called Pieraz-Cryozootech-Stallion, was born on 25 February, weighing 42kg. He will not be used for competition himself, but will instead make his living siring new generations of horses.

Pieraz, the donor of the genetic material used to create the foal, reached the top of his equestrian discipline in 1994 and 1996. He is owned by the Kanavy family of Fort Valley, Virginia, US. In 2002, Valerie Kanavy heard about cloning and immediately liked the idea that her champion could transmit his qualities to future generations despite being castrated.

And it is obvious that these scientists want to preserve the genetic heritage of this champion and of some others. They will probably make some money too.

What do you think about this cloning experiment?

Update on April 16, 2005: If you understand French, France-Info, an all-news radio station, is airing a short audio segment about this clone, with an interview with Eric Palmer, under the name “Pieraz : le deuxième cheval cloné au monde.”

Here are two links to the text version and to the audio one (RealAudio format, 1 minute and 55 seconds).

Sources: Various websites, April 2005

Related stories can be found in the following categories.

• Biotechnology
  
  
• Genetics
  
  
• Nature
  
  
• Science
  

In “Life on the Scales,” Science News recently wrote that some simple mathematical equations, known as quarter-power scaling laws, can explain the metabolic rates of living organisms. For example, “an animal’s metabolic rate appears to be proportional to mass to the 3/4 power.” And this “3/4-power law appears to hold sway from microbes to whales, creatures of sizes ranging over a mind-boggling 21 orders of magnitude.” The ecologists, physicists and chemists behind this research are now successfully applying this equation to plants, fish, full ecosystems and even biology and genetics, by adding a new key parameter: temperature. Please read this fascinating article for many more details and references. But save some time to read another long article, “Ecology’s Big, Hot Idea,” published by PLoS Biology, which states that “the way life uses energy is a unifying principle for ecology in the same way that genetics underpins evolutionary biology.” Read more…

The Science News article starts with a simple observation. Although a mouse has a shorter life than an elephant, both clock approximately the same number of heartbeats during their lives. Simply, their metabolisms are different. Now, let’s go back several decades ago.

Scientists have long known that most biological rates appear to bear a simple mathematical relationship to an animal’s size: They are proportional to the animal’s mass raised to a power that is a multiple of 1/4. These relationships are known as quarter-power scaling laws. For instance, an animal’s metabolic rate appears to be proportional to mass to the 3/4 power, and its heart rate is proportional to mass to the –1/4 power.

In subsequent decades, biologists have found that the 3/4-power law appears to hold sway from microbes to whales, creatures of sizes ranging over a mind-boggling 21 orders of magnitude.

But nobody had an explanation for this scaling law – until 1997.

The beginnings of an explanation came in 1997, when ecologist James Brown of the University of New Mexico in Albuquerque, physicist Geoffrey West of Los Alamos (N.M.) National Laboratory, and Brian Enquist, an ecologist at the University of Arizona in Tucson, described metabolic scaling in mammals and birds in terms of the geometry of their circulatory systems. It turns out, West says, that Rubner was on the right track in comparing surface area with volume, but that an animal’s metabolic rate is determined not by how efficiently it dissipates heat through its skin but by how efficiently it delivers fuel to its cells.

The idea, West says, is that a space-filling surface scales as if it were a volume, not an area. If you double each of the dimensions of your laundry machine, he observes, then the amount of linens you can fit into it scales up by 2³, not 2². Thus, an animal’s effective surface area scales as if it were a three-dimensional, not a two-dimensional, structure.

This law also can be applied to plants, fish, or even cancer growth rates — providing you add a new parameter: temperature.

In 2001, after James Gillooly, a specialist in body temperature, joined Brown at the University of New Mexico, the researchers and their collaborators presented their master equation, which incorporates the effects of size and temperature. An organism’s metabolism, they proposed, is proportional to its mass to the 3/4 power times a function in which body temperature appears in the exponent.

When the researchers filter out the effects of body temperature, most species adhere closely to quarter-power laws for a wide range of properties, including not only life span but also population growth rates. The team is now applying its master equation to more life processes — such as cancer growth rates and the amount of time animals sleep.

Now, it’s time for two key quotes [which don't appear in bold characters in the original article.]

“We’ve found that despite the incredible diversity of life, from a tomato plant to an amoeba to a salmon, once you correct for size and temperature, many of these rates and times are remarkably similar,” says Gillooly.

“Metabolic rate is, in our view, the fundamental biological rate,” Gillooly says. There is a universal biological clock, he says, “but it ticks in units of energy, not units of time.”

Then the researchers applied their master equation to ecosystems such as forests, and even to evolutionary biology, trying to answer this question: “Why do the fossil record and genetic data often give different estimates of when certain species diverged?”

When the researchers use their master equation to correct for the effects of size and temperature, the genetic estimates of divergence times — including those of rats and mice — line up well with the fossil record, says Allen, one of the paper’s coauthors.

As I wrote in the introduction, don’t miss this other paper by John Whitfield in PLoS Biology on a similar subject, “Ecology’s Big, Hot Idea.” Here are the two first paragraphs.

Life is complicated. It comes in all sorts of shapes, sizes, places, and combinations, and has evolved a dizzying variety of solutions to the problem of carrying on living. Yet look inside a cell and life takes on, if not simplicity, then at least a certain uniformity — a genetic system based around nucleic acids, for example, and a common set of chemical reactions for turning food into fuel. And looked at in broad swathes, life shows striking generalities and patterns. Every mammal’s heart will beat about one billion times in its lifetime. Both within and between species, the density of a population declines in a regular way as the size of individuals increases. And the number of species in all environments declines as you move from the equator towards the poles.

Wouldn’t it be good if there were a simple theory that used life’s shared fundamentals to explain its large-scale regularities, via its diversity of individuals? In the past few years, a team of ecologists and physicists have come up with just such a theory. At its heart is metabolism: the way life uses energy is, they claim, a unifying principle for ecology in the same way that genetics underpins evolutionary biology. They believe that energy use, in the form of metabolic rate, can be understood from the first principles of physics, and that metabolic rate can explain growth, development, population dynamics, molecular evolution, the flux of chemicals through the environment, and patterns of species diversity — to name a few.

If you don’t have enough time today, print the two articles I mentioned and read them next weekend. I promise you will not waste your time.

Sources: Erica Klarreich, Science News, Vol. 167, No. 7, p. 106, February 12, 2005; John Whitfield, PLoS Biology, Vol. 2, Issue 12, December 14, 2004

Related stories can be found in the following categories.

• Biotechnology
  
  
• Environment
  
  
• Genetics
  
  
• Mathematics
  
  
• Nature
  
  
• Physics
  

What is responsible for the evolution of forms and shapes of living organisms? Is this our genes or the DNA mechanisms which control where genes are used in the making of the animal’s body? Scientists from the University of Wisconsin-Madison have found the answer by studying the various spots on the wings of a common fruit fly. In this article, they explain that molecular switches control where the pigmentation is deployed. Common genes are controlled to produce an endless array of patterns, decoration and body architecture found in animals. And it is almost certain that these molecular switches are at work in other animals, including humans. What is even more fascinating is how it works. According to the researchers, evolution is a combination of chance and ecological necessity, which selects those things that are going to be kept. It means that animals’ features are just accidents, but accidents that are preserved because they confer some kind of advantage. Read more…

By analyzing the genetic origin of a modest spot on a fruit fly wing, Howard Hughes Medical Institute (HHMI) researchers have discovered a molecular mechanism that explains, in part, how new patterns can evolve. The secret appears to be specific segments of DNA that orchestrate where proteins are used in the construction of an insect’s body.

The researchers chose to study the evolution of the wing spot on the fruit fly because it is a simple trait with a well-understood evolutionary history. While ancient fruit fly species lack the spots, said HHMI investigator Sean B. Carroll, some species that evolved later have developed them under the pressure of sexual selection. The wing spots offer a survival advantage to males, who depend on the decorations to “impress” females to choose them in the mating process.

You’ll find other pictures on this page which also contains a link to a short movie where you can see “the male fruit fly showing off his wing spots in an effort to get the attention of the ladies.” (QuickTime format, 35 seconds, 10.1 MB).

The research work has been published by Nature on February 3, 2005 under the name “Chance caught on the wing: cis-regulatory evolution and the origin of pigment patterns in Drosophila” (Vol. 433, No. 7025, Pages 481 - 487). Here is a link to the abstract.

The gain, loss or modification of morphological traits is generally associated with changes in gene regulation during development. However, the molecular bases underlying these evolutionary changes have remained elusive. Here we identify one of the molecular mechanisms that contributes to the evolutionary gain of a male-specific wing pigmentation spot in Drosophila biarmipes, a species closely related to Drosophila melanogaster. We show that the evolution of this spot involved modifications of an ancestral cis-regulatory element of the yellow pigmentation gene. This element has gained multiple binding sites for transcription factors that are deeply conserved components of the regulatory landscape controlling wing development, including the selector protein Engrailed. The evolutionary stability of components of regulatory landscapes, which can be co-opted by chance mutations in cis-regulatory elements, might explain the repeated evolution of similar morphological patterns, such as wing pigmentation patterns in flies.

Here are few more resources if you’re interested by this findings.

• Sean Carroll’s lab
  
  
• Scientists find portal to how animals evolve
  An article from the University of Wisconsin-Madison
  
  
• A news release from the University of Wisconsin-Madison
  

Sources: Howard Hughes Medical Institute, February 4, 2005, and various websites

Related stories can be found in the following categories.

• DNA
  
  
• Genetics
  
  
• Nature
  
  
• Science
  

Even if the Morse code usage has almost disappeared, it was a very efficient communication protocol. Now, researchers from several universities and drug companies in the U.K. have discovered that our cells are also using Morse-like signals to switch genes on and off. In this news release, the Biotechnology and Biological Sciences Research Council (BBSRC) writes that this discovery may have major implications for the pharmaceutical industry. Better and more efficient drugs would only deliver the signals to our cells that will activate a desired behavior. Sounds like science fiction? Read more…

This research is featured as the cover story of the January 2005 issue of Business, the quarterly magazine of the BBSRC. Here is a link to this full issue (PDF format, 32 pages, 1.08 MB). The article about “A Morse code in cells?” appears on pages 16 and 17.

Below is a picture and its legend as they appear in the magazine (Credit: BBSRC)

Composite picture showing a series of timelapse images of a neuroblastoma cell (SK-N-AS) stimulated with TNFalpha continuously for 360 minutes. The images show that in the cell, fluorescent RelA (an NF-kappaB protein) moves into and out of the nucleus three times. Individual pictures of the cell were superimposed over a graph (subsequently removed) that quantified the extent to which the fluorescent protein is localised in the nucleus versus the cytoplasm at different times after stimulation.

Now, let’s move to the essential details of the BBSRC news release.

Morse code is a simple, effective and clear method of communication and now scientists believe that cells in our body may also be using patterns of signals to switch genes on and off. The discovery may have major implications for the pharmaceutical industry as the signalling molecules that are targeted by drugs may have more than one purpose. The number of ‘dots and dashes’ being used by each signal could have different purposes, all of which could be modified by a drug.

The researchers, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and working at the Universities of Liverpool and Manchester and the Royal Liverpool Children’s Hospital, in collaboration with scientists at AstraZeneca and Pfizer, have studied transcription factors, the signalling molecules inside cells that activate or deactivate genes. They found that the strength of the signal is less important than the dynamic frequency pattern that is used.

The researchers focused on the response of a transcription factor involved in controlling the crucial processes of cell division and cell death. They found that the dynamics of the signalling molecule resemble the changes in calcium levels that encode other messages in cells. The results suggest how common signalling molecules could convey different messages through different frequencies.

Below is a series of pictures showing the results of an experiment which lasted several hours (Credit: BBSRC)

Neuroblastoma (SK-N-AS) cells, expressing EGFP (green) and RelA-Ds-Red (red), showing repeated movements of RelA-DsRed (RelA/p65 is an NF-êB subunit) between the cytoplasm and nucleus following treatment of the cells with TNFá (Time = minutes)

And here is the conclusion of Professor Julia Goodfellow, BBSRC Chief Executive.

This research is an example of a multi-disciplinary approach producing vitally important results. By combining expertise in cell biology, chemistry, mathematical modelling and bio-imaging the research team have discovered this coded signal that is going to inform the development of better, more effective drugs.

Sources: BBSRC news release, January 10, 2005; BBSRC website

Related stories can be found in the following categories.

• Biotechnology
  
  
• Chemistry
  
  
• Genetics
  
  
• Medicine